Debrisoquine and S-mephenytoin hydroxylation polymorphisms in a Russian population living in Estonia.
OBJECTIVE
To investigate the CYP2D6 and CYP2C19 phenotypes and genotypes in a Russian population of Estonia.


METHODS
Two hundred and eighteen unrelated healthy subjects of Russian origin were studied. All participants took 10 mg debrisoquine and 100 mg S/R-mephenytoin for phenotyping. The CYP2D6 genotype was analysed by PCR amplification for the CYP2D6*3 and CYP2D6*4 alleles and subjects with S/R-mephenytoin ratios of greater than 0.5 were genotyped with respect to CYP2C19*2 and CYP2C19*3 alleles.


RESULTS
Seventeen subjects (7.8%) were classified as poor metabolisers of debrisoquine and 5 (2.3%) as poor metabolisers of S-mephenytoin. The frequency of CYP2D6*4 was 14.4% and that of CYP2D6*3 1.4%. Seven of 15 poor metabolisers of debrisoquine (47%) carried two defective CYP2D6 alleles (CYP2D6*3 or CYP2D6*4). Six of the 10 S-mephenytoin poor-metaboliser alleles (60%) carried either the CYP2C19*2 or CYP2C19*3.


CONCLUSIONS
The frequencies of poor metabolisers of debrisoquine and S-mephenytoin among Russians were similar to those in other Caucasian populations. The CYP2D6 poor-metaboliser phenotype was predicted by PCR-based amplification for the CYP2D6*3 and CYP2D6*4 alleles with 47% accuracy. The frequency of the CYP2D6*4 allele was lower in Russians than in other Caucasian populations studied so far.
Marandi
T
T
Department of Pharmacology, University of Tartu, Estonia.
Dahl
M L
ML
Rägo
L
L
Kiivet
R
R
Sjöqvist
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008617:Mephenytoin / Q000378:metabolism*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D008617:Mephenytoin; D003647:Debrisoquin